Outline

The adventitia of the vasculature of adipose tissue harbours mesenchymal stem cells with potent regenerative capacity, the so-called Adipose Tissue-derived Stem Cells (ADSC). In practice, ADSC are isolated as the plastic-adherent cells in the stromal vascular fraction of fat tissue. Their frequency is around 100x106 per litre of lipoaspirated fat. ADSC can differentiate into multiple lineages including fat, bone, cartilage, smooth muscle cells and pericytes. Yet, their main virtue resides in the secretion of a plethora of paracrine factors such as cytokines, chemokines, growth factors and non-proteinaceous factors that greatly augment healing of damaged tissues. Among others these factors are anti-inflammatory, pro-angiongenic and anti-apoptotic factors, factors that promote proliferation and furthermore factors that promote remodelling of extracellular matrix. ADSC have been successfully employed in various regenerative medicine-based strategies that range from tissue-engineering of bone and cartilage to cardiovascular repair.

Plastic surgeons have long noted that lipotransfers reduce local scars and rejuvenate skin. We hypothesized that the ADSC present in fat, have scar-reducing i.e.anti-fibrotic potential. Scars are predominantly produced by excessive matrix production by myofibroblasts in the skin. This process is mediated by the pro-fibrotic growth factor TGFb. We tested our hypothesis by subjecting differentiating (i.e. TGFb treated) human dermal fibroblasts (HDF) to conditioned culture media of ADSC (ADSCcm). We showed that ADSCcm not only suppressed the TGFb-driven differentiation of HDF, but that also their contractile activity was reduced significantly. Furthermore, ADSCcm reduced the production and secretion of extracellular matrix by HDF, while the secretion of active matrix remodelling enzymes (MMP1, 2, 3 and 9) was upregulated.

We conclude that ADSC may be suitable therapeutic cells to harness (hypertrophic) scarring.